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http://bura.brunel.ac.uk/handle/2438/19629
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DC Field | Value | Language |
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dc.contributor.author | Vivanco, I | - |
dc.contributor.author | Chen, ZC | - |
dc.contributor.author | Tanos, B | - |
dc.contributor.author | Oldrini, B | - |
dc.contributor.author | Hsieh, W-Y | - |
dc.contributor.author | Yannuzzi, N | - |
dc.contributor.author | Campos, C | - |
dc.contributor.author | Mellinghoff, IK | - |
dc.date.accessioned | 2019-11-19T12:38:46Z | - |
dc.date.available | 2019-11-19T12:38:46Z | - |
dc.date.issued | 2014 | - |
dc.identifier.citation | eLife, 3 | en_US |
dc.identifier.issn | http://dx.doi.org/10.7554/elife.03751 | - |
dc.identifier.issn | 2050-084X | - |
dc.identifier.uri | http://bura.brunel.ac.uk/handle/2438/19629 | - |
dc.description.abstract | The serine–threonine kinase AKT regulates proliferation and survival by phosphorylating a network of protein substrates. In this study, we describe a kinase-independent function of AKT. In cancer cells harboring gain-of-function alterations in MET, HER2, or Phosphatidyl-Inositol-3-Kinase (PI3K), catalytically inactive AKT (K179M) protected from drug induced cell death in a PH-domain dependent manner. An AKT kinase domain mutant found in human melanoma (G161V) lacked enzymatic activity in vitro and in AKT1/AKT2 double knockout cells, but promoted growth factor independent survival of primary human melanocytes. ATP-competitive AKT inhibitors failed to block the kinase-independent function of AKT, a liability that limits their effectiveness compared to allosteric AKT inhibitors. Our results broaden the current view of AKT function and have important implications for the development of AKT inhibitors for cancer. | en_US |
dc.description.sponsorship | National Institutes of Health (1R01NS080944–01, U54CA143798, F32 GM096558), the James S McDonnell Foundation, and National Brain Tumor Society Defeat GBM initiative | en_US |
dc.language | en | - |
dc.language.iso | en | en_US |
dc.publisher | eLife Sciences Publications, Ltd | en_US |
dc.title | A kinase-independent function of AKT promotes cancer cell survival | en_US |
dc.type | Article | en_US |
dc.identifier.doi | http://dx.doi.org/10.7554/elife.03751 | - |
dc.relation.isPartOf | eLife | - |
pubs.publication-status | Published online | - |
pubs.volume | 3 | - |
dc.identifier.eissn | 2050-084X | - |
Appears in Collections: | Dept of Life Sciences Research Papers |
Files in This Item:
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FullText.pdf | 2.12 MB | Adobe PDF | View/Open |
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